NT-proBNP level before primary PCI and risk of poor myocardial reperfusion: Insight from the On-TIME II trial.

Background N-terminal fragment of the brain natriuretic peptide prohormone (NT-proBNP), a marker for neurohumoral activation, has been associated with adverse outcome in patients with myocardial infarction. NT-proBNP levels may reflect extensive ischemia and microvascular damage, therefore we investigated the potential association between baseline NTproBNP level and ST-resolution (STR), a marker of myocardial reperfusion, after primary percutaneous coronary intervention (pPCI).Methods we performed a post-hoc analysis of the On-TIME II trial (which randomized ST-elevation myocardial infarction (STEMI) patients to pre-hospital tirofiban administration vs placebo). Patients with measured NT-proBNP before angiography were included. Multivariate logistic-regression analyses was performed to investigate the association between baseline NTproBNP level and STR one hour after pPCI.Results Out of 984 STEMI patients, 918 (93.3%) had NT-proBNP values at baseline. Patients with STR 70% had higher NT-proBNP values compared to patients with complete STR (70%) [Mean +/- SD 375.2 +/- 1021.7 vs 1007.4 +/- 2842.3, Median (IQR) 111.7 (58.4-280.0) vs 168.0 (62.3-601.3), P < .001]. At multivariate logistic regression analysis, independent predictors associated with higher risk of poor myocardial reperfusion (STR < 70%) were: NT-proBNP (OR 1.17, 95%CI 1.041.31, P = .009), diabetes mellitus (OR 1.87, 95%CI 1.14-3.07, P = .013), anterior infarct location (OR 2.74, 95% CI 2.00-3.77, P < .001), time to intervention (OR 1.06, 95%CI 1.01-1.11, P = .021), randomisation to placebo (OR 1.45, 95%CI 1.05-1.99, P = .022).Conclusions In STEMI patients, higher baseline NT-proBNP level was independently associate with higher risk of poor myocardial reper fusion, suppor ting the potential use of NT-proBNP as an early marker for risk stratification of myocardial reperfusion after pPCI in STEMI patients

Определение интервалов квазистационарности экономических систем

В работе рассмотрен вопрос определения оптимального интервала адаптации алгоритма динамического управления капиталом для нестационарного случая методами расчета показателя Херста и построения автокорреляционной функции для анализа временных рядов. Проведен анализ влияния выбора интервала адаптации на эффективность алгоритма. Из анализа полученных результатов следует, что метод расчета показателя Херста позволяет более эффективно, чем метод построения автокорреляционной функции, определить интервал стационарности модели функционирования экономической системы.Робота присвячена питанню визначення оптимального інтервалу адаптації алгоритму динамічного керування капіталом для нестаціонарного випадку за допомогою методів розрахунку показника Херста і побудови автокореляційної функції задля аналізу часових рядів. Проведено аналіз впливу вибору інтервалу адаптації на ефективність алгоритму. Порівняння результатів проведеного аналізу дозволяє стверджувати, що метод розрахунку показника Херста дозволяє більш ефективно, ніж метод побудови автокореляційної функції, визначити інтервал стаціонарності моделі функціонування економічної системи

Effect of Pre-Hospital Ticagrelor During the First 24 Hours After Primary PCI in Patients With ST-Segment Elevation Myocardial Infarction: The ATLANTIC-H Analysis

OBJECTIVES: The aim of this landmark exploratory analysis, ATLANTIC-H24, was to evaluate the effects of pre-hospital ticagrelor during the first 24 h after primary percutaneous coronary intervention (PCI) in the ATLANTIC (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery study). BACKGROUND: The ATLANTIC trial in patients with ongoing ST-segment elevation myocardial infarction showed that pre-hospital ticagrelor was safe but did not improve pre-PCI coronary reperfusion compared with in-hospital ticagrelor. We hypothesized that the effect of pre-hospital ticagrelor may not have manifested until after PCI due to the rapid transfer time (31 min). METHODS: The ATLANTIC-H24 analysis included 1,629 patients who underwent PCI, evaluating platelet reactivity, Thrombolysis In Myocardial Infarction grade 3 flow, >/=70% ST-segment elevation resolution, and clinical endpoints over the first 24 h. RESULTS: Following PCI, largest between-group differences in platelet reactivity occurred at 1 to 6 h; coronary reperfusion rates numerically favored pre-hospital ticagrelor, and the degree of ST-segment elevation resolution was significantly greater in the pre-hospital group (median, 75.0% vs. 71.4%, p = 0.049). At 24 h, the composite ischemic endpoint was lower with pre-hospital ticagrelor (10.4% vs. 13.7%, p = 0.039), as were individual endpoints of definite stent thrombosis (p = 0.0078) and myocardial infarction (p = 0.031). All endpoints except death (1.1% vs. 0.2%, p = 0.048) favored pre-hospital ticagrelor, with no differences in bleeding events. CONCLUSIONS: The effects of pre-hospital ticagrelor became apparent after PCI, with numerical differences in platelet reactivity and immediate post-PCI reperfusion, associated with reductions in ischemic endpoints, over the first 24 h, whereas there was a small excess of mortality. (Administration of Ticagrelor in the cath Lab or in the Ambulance for New ST elevation myocardial infarction to open the Coronary artery [ATLANTIC, NCT01347580])

Cost Effectiveness of a CYP2C19 Genotype-Guided Strategy in Patients with Acute Myocardial Infarction:Results from the POPular Genetics Trial

INTRODUCTION: The POPular Genetics trial demonstrated that a CYP2C19 genotype-guided P2Y12 inhibitor strategy reduced bleeding rates compared with standard treatment with ticagrelor or prasugrel without increasing thrombotic event rates after primary percutaneous coronary intervention (PCI). OBJECTIVE: In this analysis, we aimed to evaluate the cost effectiveness of a genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel. METHODS: A 1-year decision tree based on the POPular Genetics trial in combination with a lifelong Markov model was developed to compare costs and quality-adjusted life-years (QALYs) between a genotype-guided and a standard P2Y12 inhibitor strategy in patients with myocardial infarction undergoing primary PCI. The cost-effectiveness analysis was conducted from a Dutch healthcare system perspective. Within-trial survival and utility data were combined with lifetime projections to evaluate lifetime cost effectiveness for a cohort of 1000 patients. Costs and utilities were discounted at 4 and 1.5%, respectively, according to Dutch guidelines for health economic studies. Besides deterministic and probabilistic sensitivity analyses, several scenario analyses were also conducted (different time horizons, different discount rates, equal prices for P2Y12 inhibitors, and equal distribution of thrombotic events between the two strategies). RESULTS: Base-case analysis with a hypothetical cohort of 1000 subjects demonstrated 8.98 QALYs gained and €725,550.69 in cost savings for the genotype-guided strategy (dominant). The deterministic and probabilistic sensitivity analysis confirmed the robustness of the model and the cost-effectiveness results. In scenario analyses, the genotype-guided strategy remained dominant. CONCLUSION: In patients undergoing primary PCI, a CYP2C19 genotype-guided strategy compared with standard treatment with ticagrelor or prasugrel resulted in QALYs gained and cost savings. TRIAL REGISTRATION: Clinicaltrials.gov number: NCT01761786, Netherlands trial register number: NL2872

Aspirin with or without Clopidogrel after Transcatheter Aortic-Valve Implantation

BACKGROUND The effect of single as compared with dual antiplatelet treatment on bleeding and thromboembolic events after transcatheter aortic-valve implantation (TAVI) in patients who do not have an indication for long-term anticoagulation has not been well studied. METHODS In a randomized, controlled trial, we assigned a subgroup of patients who were undergoing TAVI and did not have an indication for long-term anticoagulation, in a 1:1 ratio, to receive aspirin alone or aspirin plus clopidogrel for 3 months. The two primary outcomes were all bleeding (including minor, major, and life-threatening or disabling bleeding) and non-procedure-related bleeding over a period of 12 months. Most bleeding at the TAVI puncture site was counted as non-procedure-related. The two secondary outcomes were a composite of death from cardiovascular causes, non-procedure-related bleeding, stroke, or myocardial infarction (secondary composite 1) and a composite of death from cardiovascular causes, ischemic stroke, or myocardial infarction (secondary composite 2) at 1 year, with both outcomes tested sequentially for noninferiority (noninferiority margin, 7.5 percentage points) and superiority. RESULTS A total of 331 patients were assigned to receive aspirin alone and 334 were assigned to receive aspirin plus clopidogrel. A bleeding event occurred in 50 patients (15.1%) receiving aspirin alone and in 89 (26.6%) receiving aspirin plus clopidogrel (risk ratio, 0.57; 95% confidence interval [CI], 0.42 to 0.77; P=0.001). Non-procedure-related bleeding occurred in 50 patients (15.1%) and 83 patients (24.9%), respectively (risk ratio, 0.61; 95% CI, 0.44 to 0.83; P=0.005). A secondary composite 1 event occurred in 76 patients (23.0%) receiving aspirin alone and in 104 (31.1%) receiving aspirin plus clopidogrel (difference, −8.2 percentage points; 95% CI for noninferiority, −14.9 to −1.5; P<0.001; risk ratio, 0.74; 95% CI for superiority, 0.57 to 0.95; P=0.04). A secondary composite 2 event occurred in 32 patients (9.7%) and 33 patients (9.9%), respectively (difference, −0.2 percentage points; 95% CI for noninferiority, −4.7 to 4.3; P=0.004; risk ratio, 0.98; 95% CI for superiority, 0.62 to 1.55; P=0.93). A total of 44 patients (13.3%) and 32 (9.6%), respectively, received oral anticoagulation during the trial. CONCLUSIONS Among patients undergoing TAVI who did not have an indication for oral anticoagulation, the incidence of bleeding and the composite of bleeding or thromboembolic events at 1 year were significantly less frequent with aspirin than with aspirin plus clopidogrel administered for 3 months

Less bleeding by omitting aspirin in non-ST-segment elevation acute coronary syndrome patients: Rationale and design of the LEGACY study

BACKGROUND: Early aspirin withdrawal, also known as P2Y12-inhibitor monotherapy, following percutaneous coronary intervention (PCI) for non-ST-segment elevation acute coronary syndrome (NSTE-ACS) can reduce bleeding without a trade-off in efficacy. Still the average daily bleeding risk is highest during the first months and it remains unclear if aspirin can be omitted immediately following PCI. METHODS: The LEGACY study is an open-label, multicenter randomized controlled trial evaluating the safety and efficacy of immediate P2Y12-inhibitor monotherapy versus dual antiplatelet therapy (DAPT) for 12 months in 3,090 patients. Patients are randomized immediately following successful PCI for NSTE-ACS to 75-100 mg aspirin once daily versus no aspirin. The primary hypothesis is that immediately omitting aspirin is superior to DAPT with respect to major or minor bleeding defined as Bleeding Academic Research Consortium type 2, 3, or 5 bleeding, while maintaining noninferiority for the composite of all-cause mortality, myocardial infarction and stroke compared to DAPT. CONCLUSIONS: The LEGACY study is the first randomized study that is specifically designed to evaluate the impact of immediately omitting aspirin, and thus treating patients with P2Y12-inhibitor monotherapy, as compared to DAPT for 12 months on bleeding and ischemic events within 12 months following PCI for NSTE-ACS

Evolving concepts in the management of antithrombotic therapy in patients undergoing transcatheter aortic valve implantation

Thromboembolic and bleeding complications negatively impact recovery and survival after transcatheter aortic valve implantation (TAVI). Particularly, there is a considerable risk of ischaemic stroke and vascular access related bleeding, as well as spontaneous gastro-intestinal bleeding. Therefore, benefit and harm of antithrombotic therapy should be carefully balanced. This review summarizes current evidence on peri- and post-procedural antithrombotic treatment. Indeed, in recent years, the management of antithrombotic therapy after TAVI has evolved from intensive, expert opinion-based strategies, towards a deescalated, evidence-based approach. Besides per procedural administration of unfractionated heparin, this encompasses single antiplatelet therapy in patients without a concomitant indication for oral anticoagulation (OAC); and OAC monotherapy in patients with such indication, mainly being atrial fibrillation. Combination therapy should generally be avoided to reduce bleeding risk, except after recent coronary stenting where a period of dual antiplatelet therapy (aspirin plus P2Y12-inhibitor) or P2Y12-inhibitor plus OAC (in patients with an independent indication for OAC) is recommended to prevent stent thrombosis. This new paradigm in which reduced antithrombotic intensity leads to improved patient safety, without a loss of efficacy, may be particularly suitable for elderly and fragile patients. Whether this holds in upcoming populations of younger and lower-risk patients and in specific populations as patients with subclinical valve thrombosis, is yet to be proven. Finally, whether less intensive or alternative approaches should be also applied for the periprocedural management of the antithrombotic therapy, has to be determined by ongoing and future studies

A Comparison of Measures of Endothelial Function in Patients with Peripheral Arterial Disease and Age and Gender Matched Controls

This study compared flow-mediated dilatation (FMD), peripheral artery tonometry (PAT), and serum nitric oxide (NO) measures of endothelial function in patients with peripheral artery disease (PAD) against age/gender matched controls. 25 patients (mean age: 72.4 years, M : F 18 : 7) with established PAD and an age/gender matched group of 25 healthy controls (mean age: 72.4 years, M : F 18 : 7) were studied. Endothelial function was measured using the % FMD, reactive hyperemia index (RHI) using PAT and serum NO (μmol). Difference for each method between PAD and control patients and correlation between the methods were investigated. FMD and RHI were lower in patients with PAD (median FMD for PAD = 2.16% versus control = 3.77%, p=0.034 and median RHI in PAD = 1.64 versus control = 1.92, p=0.005). NO levels were not significantly different between the groups (PAD median = 7.70 μmol, control median = 13.05 μmol, p=0.662). These results were obtained in elderly patients and cannot be extrapolated to younger individuals. FMD and PAT both demonstrated a lower hyperaemic response in patients with PAD; however, FMD results in PAD patients were unequivocally reduced whereas half the PAD patients had RHI values above the established threshold for endothelial dysfunction. This suggests that FMD is a more appropriate method for the measurement of NO-mediated endothelial function

Critical Analysis of Thrombocytopenia Associated With Glycoprotein IIb/IIIa Inhibitors and Potential Role of Zalunfiban, a Novel Small Molecule Glycoprotein Inhibitor, in Understanding the Mechanism(s)

Thrombocytopenia is a rare but serious complication of the intravenous glycoprotein IIb/IIIa (GPIIb/IIIa; integrin αIIbβ3) receptor inhibitors (GPIs), abciximab, eptifibatide, and tirofiban. The thrombocytopenia ranges from mild (50 000–100 000 platelets/μL), to severe (20 000 to <50 000/μL), to profound (<20 000/μL). Profound thrombocytopenia appears to occur in <1% of patients receiving their first course of therapy. Thrombocytopenia can be either acute (<24 hours) or delayed (up to ~14 days). Both hemorrhagic and thrombotic complications have been reported in association with thrombocytopenia. Diagnosis requires exclusion of pseudothrombocytopenia and heparin‐induced thrombocytopenia. Therapy based on the severity of thrombocytopenia and symptoms may include drug withdrawals and treatment with steroids, intravenous IgG, and platelet transfusions. Abciximab‐associated thrombocytopenia is most common and due to either preformed antibodies or antibodies induced in response to abciximab (delayed). Readministration of abciximab is associated with increased risk of thrombocytopenia. Evidence also supports an immune basis for thrombocytopenia associated with the 2 small molecule GPIs. The latter bind αIIbβ3 like the natural ligands and thus induce the receptor to undergo major conformational changes that potentially create neoepitopes. Thrombocytopenia associated with these drugs is also immune‐mediated, with antibodies recognizing the αIIbβ3 receptor only in the presence of the drug. It is unclear whether the antibody binding depends on the conformational change and whether the drug contributes directly to the epitope. Zalunfiban, a second‐generation subcutaneous small molecule GPI, does not induce the conformational changes; therefore, data from studies of zalunfiban will provide information on the contribution of the conformational changes to the development of GPI‐associated thrombocytopenia